inMIND: A phase 3 study of tafasitamab plus lenalidomide and rituximab versus placebo plus lenalidomide and rituximab for relapsed/refractory follicular or marginal zone lymphoma.
Authors: Laurie Helen Sehn, Kai Hübel, Stefano Luminari, Antonio Salar, Bjorn E. Wahlin, Ajay K. Gopal, Christophe Marc Bonnet, Shankara Paneesha, Marek Trneny, Hafsat Umar Mashegu, Christine Francis Lihou, Di Li, Christian W. Scholz
Journal: Journal of Clinical Oncology (2022)

TPS7583 Background: Most patients with the indolent non-Hodgkin lymphoma (NHL) subtypes follicular (FL) or marginal zone (MZL) respond to first-line treatment but relapse is common, and there is no single standard treatment for patients (pts) with relapsed/refractory (R/R) FL or MZL. Tafasitamab (TAFA) is an Fc-engineered humanized monoclonal antibody (mAb) against CD19 which is broadly expressed in FL and MZL, and regulates B-cell proliferation via B-cell receptor signaling. In preclinical studies, TAFA has shown activity against NHL cell lines in combination with rituximab (anti-CD20 mAb) and lenalidomide (LEN). Monotherapy with TAFA has shown promising clinical activity in a phase 2a study in pts with R/R NHL (NCT01685008), with an ORR of 29% (n/N = 10/34) in pts with FL and 33% (n/N = 3/9) in pts with MZL. In an ongoing phase 2, single-arm study (L-MIND, NCT02399085), TAFA + LEN followed by TAFA alone demonstrated an ORR of 57.5% (n/N = 46/80) in pts with R/R diffuse large B-cell lymphoma (FDA approved indication). These preclinical and clinical observations from phase 2 trials suggest a potential clinical benefit of TAFA + LEN and rituximab for pts with R/R FL or MZL. Methods: This phase 3 double-blind, placebo-controlled, randomized study is designed to investigate whether TAFA + LEN and rituximab provides improved clinical benefit compared with LEN and rituximab in pts with R/R FL or R/R MZL. Pts will be randomized 1:1 to receive TAFA (12 mg/kg IV on days 1, 8, 15, and 22 of a 28-day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) + LEN (20 mg PO QD, days 1–21/cycle for 12 cycles) and rituximab (375 mg/m 2 IV on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2–5), or placebo (0.9% saline solution IV) + LEN and rituximab. Stratified randomization will be performed separately for pts with R/R FL and R/R MZL. The primary study endpoint is PFS (investigator assessed [INV] by Lugano 2014 criteria) for pts with FL. Key secondary endpoints are PFS (INV) in overall population (FL and MZL), PET-CR rate (INV) at end of treatment (90 days after last treatment) and OS in pts with FL. Inclusion criteria include age ≥18 y, histologically confirmed FL (grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented R/R disease, ≥1 prior systemic anti-CD20 therapy (including pts with anti-CD20 refractory disease), ECOG PS ≤2, adequate systemic organ function, and high tumor burden (per GELF criteria). Exclusion criteria include prior rituximab + LEN treatment, history of radiotherapy for other diseases (≥25% of bone marrow), nonhematologic malignancy, congestive heart failure (LVEF &lt; 50%), active systemic infection, known CNS lymphoma, or severe immunocompromised state. inMIND (NCT04680052, EudraCT2020-004407-13) is currently enrolling pts; planned enrollment is 528 pts with R/R FL and 60–90 pts with R/R MZL across North America, Europe, and Asia Pacific. Clinical trial information: NCT04680052 / EudraCT2020-004407-13.